The HIV/AIDS epidemic remains one of the major global health challenges of al time. Currently over 42 million people are living with HIV and, without access to therapy, most will die of AIDS in the next 2 decades. Since 1996, potent antiretroviral therapies in the developed world have made HIV a chronic, manageable disease. For poorer settings, where 95% of the 5 million annual incident infections occur, access to interventions to treat or prevent HIV are limited. There is a great need for both innovative HIV preventive research, that includes adolescent populations, as well as therapeutic research that strives to reduce the burden of disease in poor communities. Based in South Africa, the University of the Witwatersrand's Perinatal HIV Research Unit and its key partner, the Respiratory and Meningeal Pathogens Research Unit are joint applicants in a Soweto Clinical Trials Unit (CTU).This CTU together with four clinical trial research sites (CRS) address the high priority areas of the four Network Leadership Groups of the HVTN, IMPAACT, ACTG and HPTN. This team brings extensive scientific and clinical trial experience to the new network leadership groups, has a long history of community engagement, and has developed previously disadvantaged researchers. As experienced trialists in the HVTN, they propose to contribute to the HVTN's priority research agenda by leading vaccine development teams, conducting phase l/ll trials, proof of concept trials in high risk populations and prioritizing adolescent involvement in vaccine research; as pioneers in the field of PMTCT and pediatric therapeutic and co-morbidity research, they will be instrumental in achieving the IMPAACT's agenda in optimizing PMTCT strategies and treatment strategies for children; as investigators in ground breaking prevention research that prioritizes gender and community issues, they will be able to address the HPTN's research priorities; and as researchers involved in HIV therapeutic trials in adults since 1996, in industry-funded, investigator-driven and NIH network affiliated research, they will address the ACTG's specific scientific aims of translational research/drug development, optimization of clinical management and co-morbidities, PMTCT, prevention of HIV-1 infection and therapeutic vaccine development. This research will impact on the burden of HIV in southern Africa by focusing on prevention of new infections and optimizing care of those infected with HIV. ADMINISTRATIVE COMPONENT: